The unraveling of the human genome and that of many other organisms has opened new opportunities for basic and applied research aimed at elucidating the molecular basis of disease and novel therapeutics. These studies are supported by the Structural Biology Facility, which embraces the fields of X-ray crystallography and nuclear magnetic resonance spectroscopy (NMR) to study macromolecular structures and interactions. The facility will play an important role in the Cancer Center Drug Discovery Initiative, both in target discovery and validation. The Institute has made major investments in instrumentation for this facility, including two new NMR instruments and a major upgrade for X-ray crystallography. At the interface between basic cancer biology and molecular biophysics, the Structural Biology Facility provides a means for scientists at the Cancer Center to advance their understanding of the molecular basis of complex cell-signaling pathways that are implicated in the development of human diseases. The fruits of these efforts are becoming evident with many structures solved, several of which resulted in high profile publications. These studies are also enabling the discovery and development of potential lead compounds that hold great promise for the prevention and cure of prostate and breast cancer, for example. The Structural Biology Facility is currently supporting the research of 8 ? 10 faculty members at the Institute, which we expect to increase to 20-30 research groups over the next two years. The aims for the facility are: 1) To provide a state-of-the-art structural biology laboratory which includes an X-ray generator, detectors and several NMR spectrometers; 2) To provide guidance and training in setting-up crystallization screens and to develop strategies for improving crystal quality to a level suitable for high resolution analysis; 3) To provide guidance and training in the acquisition, processing and interpretation of a minimal set of 2D and 3D NMR experiments necessary for backbone and side-chain resonance assignments and subsequently for the determination of protein structure in solution. 4) To establish a protein expression department to provide a seamless pathway from protein expression and purification to tests for suitability for crystallographic or solution NMR structural studies within Structural Biology Facility. The department will also provide protein targets to be utilized in the Chemical Library screens.